Yinli Yang1,2,3, Ling Li1,2, Zhansheng Jiang1,3, Bin Wang1,4, Zhanyu Pan5,6,7. 1. Department of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China. 2. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. 3. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China. 4. Tianjin's Clinical Research Center for Cancer, Tianjin, China. 5. Department of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China. yylyangyinli@163.com. 6. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. yylyangyinli@163.com. 7. Tianjin's Clinical Research Center for Cancer, Tianjin, China. yylyangyinli@163.com.
Abstract
BACKGROUND: Many anti-angiogenic agents have the potential to modulate the tumor microenvironment and improve immunotherapy. Anlotinib has demonstrated anti-tumor efficacy in non-small cell lung cancer (NSCLC) in third-line clinical trials. However, its roles in immune regulation and potentially synergistic anti-tumor effect in combination with immune checkpoint inhibition remain unclear. METHODS: Here, based on a syngeneic lung cancer mouse model, the intratumoral immunological changes post-anlotinib treatment in the model were assessed. Furthermore, it was tested whether anlotinib could enhance the anti-tumor effect of αPD-1 in vivo. RESULTS: This study shows that anlotinib increased infiltration of the innate immune cells, including natural killer (NK) cells, and antigen-presenting cells (APC), which include M1-like tumor-associated macrophages (TAM) and dendritic cells (DC), whereas the percentage of M2-like TAM was dramatically reduced. Subsequently, when combined with PD-1/PD-L1 (programmed cell death 1/PD-1 ligand 1) blockade, anlotinib conferred significantly synergistic therapeutic benefits. CONCLUSIONS: Overall, these findings describe a role for anlotinib in the innate immune cells in the tumor microenvironment and a potentially synergistic anti-tumor combination with immune checkpoint inhibition.
BACKGROUND: Many anti-angiogenic agents have the potential to modulate the tumor microenvironment and improve immunotherapy. Anlotinib has demonstrated anti-tumor efficacy in non-small cell lung cancer (NSCLC) in third-line clinical trials. However, its roles in immune regulation and potentially synergistic anti-tumor effect in combination with immune checkpoint inhibition remain unclear. METHODS: Here, based on a syngeneic lung cancermouse model, the intratumoral immunological changes post-anlotinib treatment in the model were assessed. Furthermore, it was tested whether anlotinib could enhance the anti-tumor effect of αPD-1 in vivo. RESULTS: This study shows that anlotinib increased infiltration of the innate immune cells, including natural killer (NK) cells, and antigen-presenting cells (APC), which include M1-like tumor-associated macrophages (TAM) and dendritic cells (DC), whereas the percentage of M2-like TAM was dramatically reduced. Subsequently, when combined with PD-1/PD-L1 (programmed cell death 1/PD-1 ligand 1) blockade, anlotinib conferred significantly synergistic therapeutic benefits. CONCLUSIONS: Overall, these findings describe a role for anlotinib in the innate immune cells in the tumor microenvironment and a potentially synergistic anti-tumor combination with immune checkpoint inhibition.
Entities:
Keywords:
APC; Anlotinib; NK cell; PD-1; Tumor immune microenvironment
Authors: Fei Xu; Haiyan Xu; Zhiyi Wan; Guangjian Yang; Lu Yang; Xueying Wu; Jin Song; Yan Wang Journal: Front Oncol Date: 2022-01-07 Impact factor: 6.244